Volume 88 Number 2
Brief clinical and laboratmy observations
261
6. Nitzan M, Zelmanovsky S, and Tikva P: Glucose intolerance in hypernatremic rats, Diabetes 17:579, 1968. 7. ArieffAI, Doerner T, Zelig H, and Massry SG: Mechanisms
of seizures and coma in hypoglycemia: evidence for a direct effect of insulin on electrolyte transport in brain, J Clin Invest 54:654, 1974.
Hemophilus influenzae
and incubated in 10% CO2 atmosphere. Hemophilus influenzae was identified by colony morphology on chocolate agar plates, by requirement of X and V factors, and by agglutination with specific antiserum. Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli were identified by standard bacteriologic procedures. The antibiotic sensitivity of all H. influenzae isolates was determined as previously described. 19 All blood and CSF cultures from Children's Hospital Medical Center, in which pathogens were grown during the study period, were also reviewed.
bacteremia in children with sickle cell disease Joel Ward, M.D., and Arnold L. Smith, M.D.,*
Boston, Mass. I N F E c T I O N is the most common cause of hospitalization in children with sickle cell disease? Many of these infections are life threatening, with pneumococcal bacteremia receiving particular emphasis in most reports. 2 14 The risk of pneumococcal infection, although low, prompted the suggestion that continued penicillin prophylaxis is indicated in these children. 1'~ Others questioned the apparent absence of systemic Hemophilus influenzae infections in patients with sickle cell disease? ~ Our recent experience suggests that H. influenzae b is an important cause of bacteremia in children with sickle cell disease. METHODS The hospital records of all children with sickle cell disease, sickle-thalessemia, and sickle/C disease who were admitted to Children's Hospital Medical Center, Boston, during the 36-month period from January, 1972, to January, 1975, were reviewed. The diagnosis in all patients was confirmed by hemoglobin electrophoresis. In this group there were 37 patients with sickle cell disease who were admitted to the hospital 83 times during the study period. Sixty-three patients had a rectal temperature > 101~ 62 of these had one or more blood cultures. Blood was cultured in trypticase soy broth with and without thioglycolate. Cerebrospinal fluid was dripped directly into brain-heart infusion broth and on chocolate agar slants. An additional tube of CSF was transported to the bacteriology laboratory, plated onto horse blood agar, From the Division of Infectious Diseases, Department of Medicine, Children's Hospital Medical Center, and Department of Pediatrics, Harvard Medical School. *Reprint address: Division of Infectious Diseases, Children's Hospital Medical Center, 300 Longwood A re., Boston, Mass. 02115.
Abbreviations used SS: sickle cell CSF: cerebrospinal fluid RESULTS We could not identify any sickle cell patients who were hospitalized for a culture-proved infection during 1972 or 1973. In 1974, one-fourth of all admissions in sickle cell patients under four years of age was for ultimately proved sepsis (Table I). Eight children with sickle cell disease had ten episodes of bacteremia; of these, six were less than three years of age. Hernophilus influenzae b was isolated from 48 blood cultures during 1974; six of these isolates were from five sickle cell patients, all of whom were less than three years of age. This was the most common cause of proved bacterial infection in our sickle cell patients. There was one recurrence of H. influenzae bacteremia two days afier cessation of nine days of intravenous ampicillin at 200 mg/kg/day. All H. influenzae isolated were sensitive to ampicillin with minimal inhibitory concentrations < 0.4 /~g/ml. There were 44 blood isolates of Streptococcus pneumoniae in 1974; two were from patients with sickle cell disease. Each of them was less than three years of age; each one died within 24 hours of admission. One 9-yearold patient with sickle cell disease had sustained Staphylococcus aureus bacteremia. During the same period of time there was a total of 52 blood isolates of Staphylococcus aureus from the general hospital population. One 20-year-old female with sickle cell disease had E. coli bacteremia secondary to pyelonephritis. We found no episodes of meningitis, bacteriologically or histologically proved osteomyelitis, or septic arthritis in our sickle cell patients. In 18 patients with sickle/C disease there was
262
Brief clinical and laboratory observations
The Journal of Pediatrics February 1976
Table I. N u m b e r o f patients, and admissions o f sickte cell patients, and age distribution
Year 1972 1973 1974 Totalt
Number of I Hb SS [ patients/ ] number of ] Hb SS ] admissions l 11/19 20/33 17/31 37/83
Age of patients (yr)* O-415-10 2 8 9 16/33
3 7 4 9/19
l > lo 6 5 4 12/37
*Certaist patients were admitted during each of two or more years. tTotal number of patients in each age group/total number of admissions in each age group. one episode o f Streptococcus pneumoniae bacteremia secondary to pneumonia in a 5-year-old girl. In 11 patients with sickle-thalessemia disease, there were no identifiable episodes of bacteremia. Except for the 20-year-old patient, all patients had no obvious source of infection; all children less than four years of age had an admission temperature greater than 104~ The complete blood count on admission did not suggest sepsis, but a leukemoid reaction often developed after admission. F o u r blood smears obtained on ten patients on admission revealed erythrophagocytosis, and all smears contained Howell-Jolly bodies. Vasoocclusive crisis and sepsis were difficult to differentiate and the hand-foot syndrome co-existed in five children with bacteremia who were less than four years of age. Cortical vein thrombosis and a bone infarct occurred in two of the bacteremic children with sickle cell disease. DISCUSSION Ten episodes of bacteremia have been d o c u m e n t e d in children with sickle cell disease at our institution over the past three years. Contrary to other reports, the majority o f these bacteremias were due to H. influenzae b; all of them occurred in children under four years of age. The two pneumococcal bacteremias in our series accounted for the only deaths emphasizing the seriousness of this infection. In accordance with recent recommendations 17 regarding serious H. influenzae infections, we begin treating children with intravenous chloramphenicol at 100 m g / k g / day and ampicillin at 400 m g / k g / d a y . W h e n the isolate is identified as Streptococcuspneumoniae, the chloramphenicol is discontinued. When the isolate is found to be H. influenzae, we continue both drugs until antibiotic sensitivities are available; then the chloramphenicol is discontinued if the isolate is ampicillin sensitive. W e think that
this policy is necessary because ampicillin-resistant H. influenzae b has been isolated from blood cultures in this institution, and that the risk of inappropriate therapy is greater than the risk of transient suppression of erythropoiesis from chloramphenicol. The only other antibiotic to which ampicillin-resistant H. influenzae is sensitive and which has comparable clinical efficacy TM is tetracycline. The untoward effect o f tetracycline might be considered minimal in comparison to the side effects of chloramphenicol in sickle cell patients, but there is little experience with its use in these patients. Other antibiotics to which ampicillin-resistant H, influenzae are sensitive in vitro, 1~ eg, Rifampi n and erythromycin, have not been demonstrated to be o f comparable clinical efficacy.
REFERENCES
1. Barrett-Connor E: Bacterial infection and sickle cell anemia, Medicine 50:97, 1971. 2. Carrington GL: Multiple osteomyelitis due to bacillus paratyphosa B, Bull Johns Hopkins Hosp 36:428, 1925. 3. Seidenstein H: Salmonella osteomyelitis, Bull Hosp Joint Dis 6:126, 1945. 4. Hook EW, Campbell CG, Weens HS, and Cooper GR: Salmonella osteomyelitis in patients with sickle cell anemia, N Engl J Med 257:403, 1957. 5. Engh CA, Hughes JL, Abrams RC, and Bowerman JW: Osteomyelitis in the patient with sickle cell disease, J Bone Joint Surg 53-A:1, 1971. 6. Specht EE: Hemoglobinopathic salmonella osteomyelitis, Clin Orthop 79:110, 1971. 7. Robinson MG, and Watson RJ: Pneumococcal meningitis in sickle cell disease, N Engl J Med 274:1006, 1966. 8. Kabins SA, and Lerner C: Fulminant pneumococcemia and sickle cell anemia, JAMA 211:467, 1970. 9. Seeler R, Metzger W, and Mufson MA: Diplococcus pneumonia infection in children with sickle cell anemia, Am J Dis Child 123:8, 1972. 10. Seeler RB: Deaths in children with sickle cell anemia, Clin Pediatr 11:634, 1972. 11. Scott RB, and Ferguson AD: Studies in sickle cell anemia XXVII. Complications in infants and children in the United States, Clin Pediatr 5:403, 1966. 12. Porter T, and Thurman WG: Studies of sickle cell disease: Diagnosis in infancy, Am J Dis Child 106:35, 1963. 13. Shulman ST, Bartlett J, Clyde WA, and Ayoub EM: Unusual severity of mycoplasmal pneumonia in children with sickle cell disease, N Engl J Med 287:164, 1972. 14. Lukens JN: Hemoglobin S, the Pneumococcus, and the spleen, Am J Dis Child 123:6, 1972. 15. Diamond LK: Splenectomy in childhood and the hazard of overwhelming infection, Pediatrics 43:886, 1969. 16. Nelson JD: Sickle-cell disease and bacterial bone and joint infection, N Engl J Med 292:534, 1975. 17. American Academy of Pediatrics, Committee on Infectious Disease: Ampicillin-resistant strains of Hemophilus influenzae type b, Pediatrics 55:145, 1975. 18. Nelson KE, Levin S, Spies HW, and Lepper MH: Treat-
Volume 88 Number 2
Brief clinical and laboratory observations
ment of Hemophilus influenzae meningitis: A comparison of chloramphenicol and tetracycline, J Inf Dis 125:459, 1972.
263
19. Emerson BB, Smith AL, Harding AL, and Smith DH: H. influenzae b susceptibility to 17 antibiotics, J PEDIATR 86:617, 1975.
Laryngeal obstruction in childhood sarcoidosis Barbara S. Kirschner, M.D.,* and Paul H. Holinger, M.D., Chicago, 111. MORE THAN 230 CHILDREN with sarcoidosis have been described in the pediatric literature, but none had recognized laryngeal involvement resulting in significant respiratory impairment. The present c o m m u n i c a t i o n describes a 14-year-old boy who developed almost complete airway obstruction secondary to extensive laryngeal infiltration at a time when his p u l m o n a r y parenchymal disease had improved. CASE REPORT Patient R. S., a 14-year-old black male, was well until nine years of age, when he developed progressive dyspnea, cough, and anorexia. Physical findings included respiratory distress at rest, perioral cyanosis, granulomatous uveitis, cervical adenopathy, and digital dubbing, but no hepatosplenomegaly. Chest roentgenogram showed bilateral hilar and right paratracheal adenopathy, with diffuse bilateral nodular infiltrations. Results of fungal complement fixation titers, skin tests for fungi, and purified protein derivative were negative. Noncaseating, epithelioid granulomas were observed in a paratracheal lymph node biopsy; stains and cultures for acid-fast bacilli and fungi were negative. The patient received prednisone 20 mg daily for seven months followed by alternate-day therapy. Four months later, in March, 1971, hoarseness developed; on indirect laryngoscopy, vocal cords and epiglottis were normal but mild inflammation of the left arytenoid was noted. Pulmonary function studies and blood gas determinations were within normal limits. Prednisone dosage was decreased gradually, but exertional dyspnea recurred. In February, 1973, increasing dyspnea, cough, and hoarseness occurred with no evidence of increasing pulmonary disease radiologically or by pulmonary function studies. In June, 1973, swelling of the nasal turbinates ensued; biopsy showed noncaseating granulomas. Indirect laryngoscopy demon-
From the Department of Pediatrics, Michael Reese Hospital, and the Department of Laryngology and Bronchoesophagology, University of lllinois Hospital. *Reprint address: Departmentof Pediatrics, Universityof Chicago, 5825 MarylandA re., Chicago, Ill. 60637.
Fig. 1. Lateral xeroradiogram of the neck, demonstrating epiglottic edema, subglottic polypoid masses, and tracheal stenosis. strated edema of the uvula, epiglottis, and aryepiglottic folds; a chest roentgenogram was unchanged. The sudden onset of stridor in August, 1973, necessitated immediate hospitalization. The epiglottis and arytenoids were enlarged and the glottis was 80% narrowed. Soft tissue swelling in the subglottic region and narrowing in the midtrachea were apparent on the roentgenogram. A tracheotomy was planned, but was cancelled because of rapid improvement of laryngeal edema within 48 hours after 60 mg daily of prednisone. Alternate-day prednisone (80 mg) therapy was started, but within three months there was increasing hoarseness, exertional dyspnea, and mouth breathing. Xeroradiograms of the head and neck demonstrated epiglottic edema, large polypoid subglottic masses, and circumscribed stenosis of the
Brief clinical and laboratmy observations
261
6. Nitzan M, Zelmanovsky S, and Tikva P: Glucose intolerance in hypernatremic rats, Diabetes 17:579, 1968. 7. ArieffAI, Doerner T, Zelig H, and Massry SG: Mechanisms
of seizures and coma in hypoglycemia: evidence for a direct effect of insulin on electrolyte transport in brain, J Clin Invest 54:654, 1974.
Hemophilus influenzae
and incubated in 10% CO2 atmosphere. Hemophilus influenzae was identified by colony morphology on chocolate agar plates, by requirement of X and V factors, and by agglutination with specific antiserum. Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli were identified by standard bacteriologic procedures. The antibiotic sensitivity of all H. influenzae isolates was determined as previously described. 19 All blood and CSF cultures from Children's Hospital Medical Center, in which pathogens were grown during the study period, were also reviewed.
bacteremia in children with sickle cell disease Joel Ward, M.D., and Arnold L. Smith, M.D.,*
Boston, Mass. I N F E c T I O N is the most common cause of hospitalization in children with sickle cell disease? Many of these infections are life threatening, with pneumococcal bacteremia receiving particular emphasis in most reports. 2 14 The risk of pneumococcal infection, although low, prompted the suggestion that continued penicillin prophylaxis is indicated in these children. 1'~ Others questioned the apparent absence of systemic Hemophilus influenzae infections in patients with sickle cell disease? ~ Our recent experience suggests that H. influenzae b is an important cause of bacteremia in children with sickle cell disease. METHODS The hospital records of all children with sickle cell disease, sickle-thalessemia, and sickle/C disease who were admitted to Children's Hospital Medical Center, Boston, during the 36-month period from January, 1972, to January, 1975, were reviewed. The diagnosis in all patients was confirmed by hemoglobin electrophoresis. In this group there were 37 patients with sickle cell disease who were admitted to the hospital 83 times during the study period. Sixty-three patients had a rectal temperature > 101~ 62 of these had one or more blood cultures. Blood was cultured in trypticase soy broth with and without thioglycolate. Cerebrospinal fluid was dripped directly into brain-heart infusion broth and on chocolate agar slants. An additional tube of CSF was transported to the bacteriology laboratory, plated onto horse blood agar, From the Division of Infectious Diseases, Department of Medicine, Children's Hospital Medical Center, and Department of Pediatrics, Harvard Medical School. *Reprint address: Division of Infectious Diseases, Children's Hospital Medical Center, 300 Longwood A re., Boston, Mass. 02115.
Abbreviations used SS: sickle cell CSF: cerebrospinal fluid RESULTS We could not identify any sickle cell patients who were hospitalized for a culture-proved infection during 1972 or 1973. In 1974, one-fourth of all admissions in sickle cell patients under four years of age was for ultimately proved sepsis (Table I). Eight children with sickle cell disease had ten episodes of bacteremia; of these, six were less than three years of age. Hernophilus influenzae b was isolated from 48 blood cultures during 1974; six of these isolates were from five sickle cell patients, all of whom were less than three years of age. This was the most common cause of proved bacterial infection in our sickle cell patients. There was one recurrence of H. influenzae bacteremia two days afier cessation of nine days of intravenous ampicillin at 200 mg/kg/day. All H. influenzae isolated were sensitive to ampicillin with minimal inhibitory concentrations < 0.4 /~g/ml. There were 44 blood isolates of Streptococcus pneumoniae in 1974; two were from patients with sickle cell disease. Each of them was less than three years of age; each one died within 24 hours of admission. One 9-yearold patient with sickle cell disease had sustained Staphylococcus aureus bacteremia. During the same period of time there was a total of 52 blood isolates of Staphylococcus aureus from the general hospital population. One 20-year-old female with sickle cell disease had E. coli bacteremia secondary to pyelonephritis. We found no episodes of meningitis, bacteriologically or histologically proved osteomyelitis, or septic arthritis in our sickle cell patients. In 18 patients with sickle/C disease there was
262
Brief clinical and laboratory observations
The Journal of Pediatrics February 1976
Table I. N u m b e r o f patients, and admissions o f sickte cell patients, and age distribution
Year 1972 1973 1974 Totalt
Number of I Hb SS [ patients/ ] number of ] Hb SS ] admissions l 11/19 20/33 17/31 37/83
Age of patients (yr)* O-415-10 2 8 9 16/33
3 7 4 9/19
l > lo 6 5 4 12/37
*Certaist patients were admitted during each of two or more years. tTotal number of patients in each age group/total number of admissions in each age group. one episode o f Streptococcus pneumoniae bacteremia secondary to pneumonia in a 5-year-old girl. In 11 patients with sickle-thalessemia disease, there were no identifiable episodes of bacteremia. Except for the 20-year-old patient, all patients had no obvious source of infection; all children less than four years of age had an admission temperature greater than 104~ The complete blood count on admission did not suggest sepsis, but a leukemoid reaction often developed after admission. F o u r blood smears obtained on ten patients on admission revealed erythrophagocytosis, and all smears contained Howell-Jolly bodies. Vasoocclusive crisis and sepsis were difficult to differentiate and the hand-foot syndrome co-existed in five children with bacteremia who were less than four years of age. Cortical vein thrombosis and a bone infarct occurred in two of the bacteremic children with sickle cell disease. DISCUSSION Ten episodes of bacteremia have been d o c u m e n t e d in children with sickle cell disease at our institution over the past three years. Contrary to other reports, the majority o f these bacteremias were due to H. influenzae b; all of them occurred in children under four years of age. The two pneumococcal bacteremias in our series accounted for the only deaths emphasizing the seriousness of this infection. In accordance with recent recommendations 17 regarding serious H. influenzae infections, we begin treating children with intravenous chloramphenicol at 100 m g / k g / day and ampicillin at 400 m g / k g / d a y . W h e n the isolate is identified as Streptococcuspneumoniae, the chloramphenicol is discontinued. When the isolate is found to be H. influenzae, we continue both drugs until antibiotic sensitivities are available; then the chloramphenicol is discontinued if the isolate is ampicillin sensitive. W e think that
this policy is necessary because ampicillin-resistant H. influenzae b has been isolated from blood cultures in this institution, and that the risk of inappropriate therapy is greater than the risk of transient suppression of erythropoiesis from chloramphenicol. The only other antibiotic to which ampicillin-resistant H. influenzae is sensitive and which has comparable clinical efficacy TM is tetracycline. The untoward effect o f tetracycline might be considered minimal in comparison to the side effects of chloramphenicol in sickle cell patients, but there is little experience with its use in these patients. Other antibiotics to which ampicillin-resistant H, influenzae are sensitive in vitro, 1~ eg, Rifampi n and erythromycin, have not been demonstrated to be o f comparable clinical efficacy.
REFERENCES
1. Barrett-Connor E: Bacterial infection and sickle cell anemia, Medicine 50:97, 1971. 2. Carrington GL: Multiple osteomyelitis due to bacillus paratyphosa B, Bull Johns Hopkins Hosp 36:428, 1925. 3. Seidenstein H: Salmonella osteomyelitis, Bull Hosp Joint Dis 6:126, 1945. 4. Hook EW, Campbell CG, Weens HS, and Cooper GR: Salmonella osteomyelitis in patients with sickle cell anemia, N Engl J Med 257:403, 1957. 5. Engh CA, Hughes JL, Abrams RC, and Bowerman JW: Osteomyelitis in the patient with sickle cell disease, J Bone Joint Surg 53-A:1, 1971. 6. Specht EE: Hemoglobinopathic salmonella osteomyelitis, Clin Orthop 79:110, 1971. 7. Robinson MG, and Watson RJ: Pneumococcal meningitis in sickle cell disease, N Engl J Med 274:1006, 1966. 8. Kabins SA, and Lerner C: Fulminant pneumococcemia and sickle cell anemia, JAMA 211:467, 1970. 9. Seeler R, Metzger W, and Mufson MA: Diplococcus pneumonia infection in children with sickle cell anemia, Am J Dis Child 123:8, 1972. 10. Seeler RB: Deaths in children with sickle cell anemia, Clin Pediatr 11:634, 1972. 11. Scott RB, and Ferguson AD: Studies in sickle cell anemia XXVII. Complications in infants and children in the United States, Clin Pediatr 5:403, 1966. 12. Porter T, and Thurman WG: Studies of sickle cell disease: Diagnosis in infancy, Am J Dis Child 106:35, 1963. 13. Shulman ST, Bartlett J, Clyde WA, and Ayoub EM: Unusual severity of mycoplasmal pneumonia in children with sickle cell disease, N Engl J Med 287:164, 1972. 14. Lukens JN: Hemoglobin S, the Pneumococcus, and the spleen, Am J Dis Child 123:6, 1972. 15. Diamond LK: Splenectomy in childhood and the hazard of overwhelming infection, Pediatrics 43:886, 1969. 16. Nelson JD: Sickle-cell disease and bacterial bone and joint infection, N Engl J Med 292:534, 1975. 17. American Academy of Pediatrics, Committee on Infectious Disease: Ampicillin-resistant strains of Hemophilus influenzae type b, Pediatrics 55:145, 1975. 18. Nelson KE, Levin S, Spies HW, and Lepper MH: Treat-
Volume 88 Number 2
Brief clinical and laboratory observations
ment of Hemophilus influenzae meningitis: A comparison of chloramphenicol and tetracycline, J Inf Dis 125:459, 1972.
263
19. Emerson BB, Smith AL, Harding AL, and Smith DH: H. influenzae b susceptibility to 17 antibiotics, J PEDIATR 86:617, 1975.
Laryngeal obstruction in childhood sarcoidosis Barbara S. Kirschner, M.D.,* and Paul H. Holinger, M.D., Chicago, 111. MORE THAN 230 CHILDREN with sarcoidosis have been described in the pediatric literature, but none had recognized laryngeal involvement resulting in significant respiratory impairment. The present c o m m u n i c a t i o n describes a 14-year-old boy who developed almost complete airway obstruction secondary to extensive laryngeal infiltration at a time when his p u l m o n a r y parenchymal disease had improved. CASE REPORT Patient R. S., a 14-year-old black male, was well until nine years of age, when he developed progressive dyspnea, cough, and anorexia. Physical findings included respiratory distress at rest, perioral cyanosis, granulomatous uveitis, cervical adenopathy, and digital dubbing, but no hepatosplenomegaly. Chest roentgenogram showed bilateral hilar and right paratracheal adenopathy, with diffuse bilateral nodular infiltrations. Results of fungal complement fixation titers, skin tests for fungi, and purified protein derivative were negative. Noncaseating, epithelioid granulomas were observed in a paratracheal lymph node biopsy; stains and cultures for acid-fast bacilli and fungi were negative. The patient received prednisone 20 mg daily for seven months followed by alternate-day therapy. Four months later, in March, 1971, hoarseness developed; on indirect laryngoscopy, vocal cords and epiglottis were normal but mild inflammation of the left arytenoid was noted. Pulmonary function studies and blood gas determinations were within normal limits. Prednisone dosage was decreased gradually, but exertional dyspnea recurred. In February, 1973, increasing dyspnea, cough, and hoarseness occurred with no evidence of increasing pulmonary disease radiologically or by pulmonary function studies. In June, 1973, swelling of the nasal turbinates ensued; biopsy showed noncaseating granulomas. Indirect laryngoscopy demon-
From the Department of Pediatrics, Michael Reese Hospital, and the Department of Laryngology and Bronchoesophagology, University of lllinois Hospital. *Reprint address: Departmentof Pediatrics, Universityof Chicago, 5825 MarylandA re., Chicago, Ill. 60637.
Fig. 1. Lateral xeroradiogram of the neck, demonstrating epiglottic edema, subglottic polypoid masses, and tracheal stenosis. strated edema of the uvula, epiglottis, and aryepiglottic folds; a chest roentgenogram was unchanged. The sudden onset of stridor in August, 1973, necessitated immediate hospitalization. The epiglottis and arytenoids were enlarged and the glottis was 80% narrowed. Soft tissue swelling in the subglottic region and narrowing in the midtrachea were apparent on the roentgenogram. A tracheotomy was planned, but was cancelled because of rapid improvement of laryngeal edema within 48 hours after 60 mg daily of prednisone. Alternate-day prednisone (80 mg) therapy was started, but within three months there was increasing hoarseness, exertional dyspnea, and mouth breathing. Xeroradiograms of the head and neck demonstrated epiglottic edema, large polypoid subglottic masses, and circumscribed stenosis of the
